The objective of this study was to examine the short- and midterm outcomes of catheter-directed thrombolysis (CDT) for acute lower limb ischemia (ALI), classes Rutherford 1 and 2, with specific attention to functional outcome. This retrospective study included patients with ALI treated with CDT from 2 vascular centers between May 2018 and April 2021. Cases were analyzed in groups according to the Rutherford (1 and 2) classification. The primary endpoint was functional outcome during follow-up, assessed by Rutherford's chronic limb ischemia classification. Functional outcomes over time were analyzed by generalized estimating equations. Kaplan-Meier analysis was used to estimate reintervention, amputation, survival, and reintervention-free survival rates. Two hundred cases were included (Rutherford 1, n = 51; Rutherford 2, n = 149). Total median treatment duration was 27 hours in the Rutherford 1 group and 39 hours in the Rutherford 2 group (P= 0.120). Initial clinical success was high (Rutherford 1, 82% vs Rutherford 2, 89%; P= 0.253). Complications were comparable between the 2 groups: major bleeding 8% vs 10% (P= 0.634), major amputation 4% vs 7% (P= 0.603), and mortality 6% vs 6% (P= 0.967). Median follow-up was 32 months (0-63 months). During follow-up, there was a high number of reinterventions (43%) and amputations (20%) in patients with Rutherford 1 limb ischemia, which was comparable to patients with Rutherford 2 limb ischemia. Fifty-six percent of the patients with Rutherford 1 limb ischemia reaching 2 years of follow-up were asymptomatic, 20% had mild and 16% had moderate to severe claudication. Initial clinical success following CDT and not immediately threatened ischemia at presentation are associated with improved functional outcomes during follow-up (P < 0.001 and P= 0.009, respectively). In our cohort, CDT was effective in reestablishing arterial flow for not immediately threatened ALI. Patients with Rutherford 1 limb ischemia who receive CDT had a more favorable functional outcome than patients with more severe limb ischemia (Rutherford 2). However, reinterventions were required frequently, and there was a substantial risk of complications. Acute lower limb ischemia (ALI) does not immediately jeopardize limb survival in patients with Rutherford 1 limb ischemia but can induce disabling claudication. In such patients, catheter-directed thrombolysis (CDT) is often performed to improve functional outcome. However, previous reports warned about the complications of CDT, and so far, mid- and long-term functional outcomes have not been reported. This study, in which a large cohort of patients with ALI was included, demonstrates a high technical success of CDT for not immediately threatened ALI with more favorable functional outcomes when compared with those with threatened limbs. Nevertheless, major complications pose a serious risk, and the need for reinterventions in the long term is high.